The ultimate objective of this program is to develop a novel therapeutic approach that will save lives of patients with stroke. Acute stroke is the third leading cause of death in the United States and the primary medical cause of acquired adult disability. Each year, ~795,000 Americans experience new or recurrent stroke. It accounts for 1 out of every 18 deaths in the United States. As the population ages, stroke care costs are expected to increase substantially. The direct medical costs for stroke care are estimated to increase from $28.3 billion in 2010 to $95.6 billion in 2030. Despite its prevalence, current treatment options are very limited and stroke survivors still encounter serious morbidity issues. The development of safe and effective therapeutics to treat stroke patients remains a major challenge to the pharmaceutical industry. Human ghrelin, a novel gastrointestinal hormone, was first identified as the endogenous ligand for the growth hormone secretagogue receptor type 1a (i.e., ghrelin receptor). Ghrelin freely crosses the blood brain barrier (BBB) and has been reported to induce growth hormone release through stimulation of ghrelin receptor in the central nervous system. However, sufficient evidence has pointed out other physiological functions of ghrelin in addition to its role in growth hormone release. Using an animal model of permanent middle cerebral artery occlusion (i.e., ischemic stroke), our preliminary studies have shown that human ghrelin treatment improved neurological function, reduced infarct size, and increased survival. The primary objective of this project is targeted towards demonstrating the feasibility o the further development and commercialization of human ghrelin as a novel therapeutic agent for stroke patients. Animal models of ischemic stroke with or without reperfusion will be used. The optimal dosage(s) and therapeutic window will be determined by assessing the dose-dependent effect of human ghrelin on brain injury and the time-course of human ghrelin's beneficial effects after stroke. Furthermore, we will investigate the long-term effect of human ghrelin on motor function impairment after ischemic stroke with or without reperfusion. Our future goal (SBIR Phase II and beyond) is to obtain commercial utilization of human ghrelin as a safe and effective therapy for patients suffering from stroke.